The latest $540 million gift from one billionaire’s estate has brought the trust’s total philanthropy for cancer research to $2.5 billion. One of the largest single contributions to fighting the disease, funds will yield flexible, ongoing support for six of the nation’s top research universities—each with its own focus for preventing and treating cancer—at a time when many are struggling to maintain their funding.

With the announcement of the gift this week, late American shipping titan Daniel Ludwig joined the ranks of Phil Knight and Mark Zuckerberg in being behind the largest philanthropic gifts in recent history. Knight donated $500 million to cancer research as well in 2013, with a grant to Oregon Health Sciences University. The $540 million from Ludwig’s estate will be divided up equally among six previously established Ludwig Centers at prominent American research universities. The funds are being directed by Ludwig Cancer Research, which grew from an initiative Ludwig started in the 1970s.

If Ludwig’s name isn’t familiar to you, it’s not surprising. The shipping magnate was very secretive about his wealth, although in later years became something of a quirky New York personality, according to his New York Times obituary. In the 1980s, Ludwig topped Forbes’ richest Americans list due to fortunes amassed from his international shipping operation, real estate and oil and gas investments. While he tended not speak to the press during his business career, he did gain quite a bit of attention due to a failed farming and mining operation the size of Connecticut that he tried to establish in Brazilian jungle.

Ludwig passed away from heart failure in 1992, and while neither he, nor his family, had a history with cancer, he considered it a hugely important cause. He has said he donated almost all of his international holdings in the 1970s to create the Ludwig Institute for Cancer Research, which has spread to become Ludwig Cancer Research, supporting multiple research centers.

In 2006, his estate gave $120 million to create six Ludwig Centers, at Harvard, Johns Hopkins, Stanford, the University of Chicago, the Massachusetts Institute of Technology, and Memorial Sloan-Kettering Cancer Center. The latest $540 million came from the sale of New York office buildings he’s held since the 1960s, and will divvy up $90 million to go toward each center’s endowment. The investments should yield around $5 million a year that each center will put toward its own research focus.

Johns Hopkins has announced it will pursue research in diagnostics for early detection and prevention. The University of Chicago and MIT will focus on the study of metastasis, the process in which cancer cells spread from tumors to other parts of the body, leading to 90 percent of cancer deaths. Sloan-Kettering intends to spend the funding on research of immune-system-based cancer therapies. Stanford will continue its research into cancer stem cells, which generate new cancer cells. And Harvard will use its network of hospitals to study why the disease so often returns.